Effects of SGLT2 Inhibitors on Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.
SGLT2 抑制剂对 2 型糖尿病患者非酒精性脂肪肝的影响: 随机对照试验的荟萃分析。
- 作者列表："Xing B","Zhao Y","Dong B","Zhou Y","Lv W","Zhao W
BACKGROUND/OBJECTIVE:Non-alcoholic fatty liver disease (NAFLD) is more and more common in patients with type 2diabetes mellitus (T2DM). Currently, some researches have found that Sodium glucose co- transporter2 (SGLT2) inhibitors, a new hypoglycemic drug, can improve nonalcoholic fatty liver besides hypoglycemic effect. Thus, we undertook a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of SGLT2 inhibitors on the treatment of NAFLD METHODS: PubMed, Embase and the Cochrane Library were searched for RCTs of SGLT2 inhibitors in patients with NAFLD and T2DM up to Oct1, 2019. Differences were expressed as weight mean difference (WMD) with 95% CI for continuous outcomes. I2 statistic was applied to evaluate the heterogeneity of studies. RESULTS:A total of six trials including 309 patients were selected into our meta-analysis. SGLT2 inhibitors could reduce alanine amino- transferase (ALT) (WMD (95% CI): -11.05IU/L (-19.85, -2.25); P=0.01) and MRI-PDFF (WMD (95% CI): -2.07% (-3.86,-0.28); P=0.02). However, SGLT2 inhibitors didn't reduce aspartate aminotransferas (AST) (WMD (95% CI): -1.11IU/L (-2.39, 0.17); P=0.09). Besides, secondary outcomes such as body weight and visceral fat area (VFA), were also reduced (WMD (95% CI): -1.62Kg (-2.02, -1.23), P < 0.00001, WMD (95% CI): -19.98cm2 (-27.18, -12.79), P<0.00001, respectively). CONCLUSIONS:SGLT2 inhibitors can significantly decrease ALT and liver fat, accompanying with weight loss, which may have a positive effect on fatty liver in patients with T2DM. The limitation is that the sample size of the studies is small. Therefore, more large RCTs specified on NAFLD are needed to evaluate these results.
背景/目的: 非酒精性脂肪性肝病 (NAFLD) 在 2 型糖尿病 (T2DM) 患者中越来越常见。目前有研究发现，新型降糖药物钠葡萄糖共转运体 2 (SGLT2) 抑制剂除降糖作用外，还能改善非酒精性脂肪肝。因此，我们对随机对照试验 (rct) 进行了荟萃分析，以评价 SGLT2 抑制剂治疗 NAFLD 的疗效。方法: PubMed, 检索 Embase 和 Cochrane 图书馆截至 2019年10月1日 SGLT2 抑制剂在 NAFLD 和 T2DM 患者中的 rct。差异表示为体重平均差 (WMD)，连续结局的 95% CI。应用 I2 统计量评价研究的异质性。 结果: 共 6 项试验，包括 309 例患者，入选我们的荟萃分析。SGLT2 抑制剂可降低丙氨酸氨基转移酶 (ALT) (WMD (95% CI):-11。 05IU/L (-19.85，-2.25); P = 0.01) 和 MRI-PDFF (WMD (95% CI):-2.07% (-3.86，-0.28); P = 0.02)。然而，SGLT2 抑制剂没有降低天冬氨酸氨基转移酶 (AST) (WMD (95% CI):-1.11iu/L (-2.39，0.17); P = 0.09)。此外，体重和内脏脂肪面积 (VFA) 等次要结局也减少 (WMD (95% CI):-1.62 kg (-2.02，-1.23), P
METHODS:BACKGROUND:Opioids are often prescribed for pain in cirrhosis and may increase the risk of hepatic encephalopathy (HE). AIMS:To assess the association between opioids and HE in patients with well-compensated cirrhosis. METHODS:We used the IQVIA PharMetrics (Durham, NC) database to identify patients aged 18-64 years with cirrhosis. We excluded patients with any decompensation event from 1 year before cirrhosis diagnosis to 6 months after cirrhosis diagnosis. Over the 6 months after cirrhosis diagnosis, we determined the duration of continuous opioid use and classified use into short term (1-89 days) and chronic (90-180 days). We assessed whether patients developed HE over the subsequent year (ie 6-18 months after cirrhosis diagnosis). We used a landmark analysis and performed multivariable Cox proportional hazards regression to assess associations between opioid use and HE, adjusting for relevant confounders. RESULTS:The cohort included 6451 patients with compensated cirrhosis, of whom 23.3% and 4.7% had short-term and chronic opioid prescriptions respectively. Over the subsequent year, HE occurred in 6.3% patients with chronic opioid prescriptions, 5.0% with short-term opioid prescriptions and 3.3% with no opioid prescriptions. In the multivariable model, an increased risk of HE was observed with short-term (adjusted hazard ratio, HR 1.44, 95% CI 1.07-1.94) and chronic opioid prescriptions (adjusted HR 1.83, 95% CI 1.07-3.12) compared to no opioid prescriptions. CONCLUSION:In this national cohort of privately insured patients with cirrhosis, opioid prescriptions were associated with the risk of incident HE. Opioid use should be minimised in those with cirrhosis and, when required, limited to short duration.
METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.
METHODS:BACKGROUND:Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with liver cirrhosis. In recent years, it has been postulated that the rate of multidrug-resistant organisms (MDROs) is increasing, especially in nosocomial SBP patients. Aim of the present work was to investigate this hypothesis and its possible clinical consequences. MATERIALS AND METHODS:One hundred and three culture-positive patients between 2007 and 2014 were compared with 81 patients between 2015 and 2017, to study the change of microbiological profiles and their clinical consequences. The cirrhosis patients with bacterascites requiring treatment were included as well. RESULTS:The most prevalent Gram-negative bacteria isolated from ascites were Enterobacterales (31.6%) and in Gram-positive pathogens Staphylococci (22.8%). There was a significant increase in MDROs (22.3% ICU 40.7%, P = .048), accompanied by an increased incidence of sepsis (from 21.4% to 37.0%, P = .021), hepatorenal syndrome (from 40.8% to 58.0%, P = .007) and the need of catecholamine therapy (from 21.4% to 38.8%, P = .036). Nosocomial origin correlated with higher MDRO proportion, more complications and lower antimicrobial susceptibility rates in 12 commonly used antibiotics. MDROs were confirmed as an isolated predictor for inpatient mortality and complications in multivariable logistic regression. CONCLUSIONS:The feeling in clinical practice that MDROs have increased in the last 11 years could be confirmed in our study in Munich, Germany. Nosocomial SBP correlated with significantly higher MDRO rates (nearly 50%) and complication rates. In our opinion, an antibiotic combination with comprehensive effect should be taken into account in nosocomial SBP patients in this region.